In recent years, cancer has surpassed cardiovascular diseases to become the world's leading death disease, antineoplastic research has an important academic and practical significance. The study found that almost all of the tumors are related to uncontrolled cell growth, blocked differentiation and apoptosis abnormalities caused by cell cycle control mechanisms disorder.
Initiation, progression, and completion of the mammalian cell cycle are regulated by various cyclin-dependent kinase (CDK) complexes, which are critical for cell growth. These complexes comprise at least a catalytic (the CDK itself) and a regulatory (cyclin) subunit. Some of the more important complexes for cell cycle regulation include cyclin A (CDK1—also known as CDC2, and CDK2), cyclin B1-B3 (CDK1) and cyclin D1-D3 (CDK2, CDK4, CDK5, CDK6), cyclin E (CDK2). Each of these complexes is involved in a particular phase of the cell cycle. The activity of CDKs is regulated post-translationally, by transitory associations with other proteins, and by alterations of their intracellular localization. Tumor development is closely associated with genetic alteration and deregulation of CDKs and their regulators, suggesting that inhibitors of CDKs may be useful anti-cancer therapeutics.
CDKs, and their associated proteins, in co-ordinating and driving the cell cycle in proliferating cells play key roles in some biochemical pathways. Using therapeutics targeted generically at CDKs, or at specific CDKs can be for the treatment of proliferative disorders, such as cancers. CDK inhibitors could conceivably also be used to treat other conditions such as viral infections, autoimmune diseases and neuro-degenerative diseases, amongst others. CDK targeted therapeutics may also provide clinical benefits in the treatment of the previously described diseases when used in combination therapy with existing therapeutic agents. CDK targeted anticancer therapies could potentially have advantages over many current antitumour agents as they would not directly interact with DNA and should therefore reduce the risk of secondary tumour development.
Although a number of CDKs compounds have been disclosed in the art, in view of the number of pathological responses that are mediated by CDK, there remains a continuing need for drugs which can be used in the treatment of a variety of conditions mediated by CDK, especially CDK4/6.